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Extra info for Iron Metabolism, Anemias. Diagnosis and Therapy: Novel concepts in the anemias of renal and rheumatoid disease
44 Disturbances of Iron Metabolism/Erythropoiesis Hemoglobinopathies Hemoglobinopathies are a disturbance in the synthesis of the protein components of hemoglobin . A distinction is made between point mutations with exchange of individual amino acids and defects in whole protein chains. Of the former, sicklecell anemia is the most important because it is widespread in the black population of Africa and America. The substitution of valine for glutaminic acid as sixth amino acid in the ~-chain leads to the synthesis of so-called sickle-cell hemoglobin (HbS) which has a very low solubility when it is not 02 saturated.
Increased iron storage in macrophages in ACD draws iron from transferrin; in contrast to true iron overload, this kind of iron redistribution is characterized by a low transferrin saturation. Cytokine induced iron uptake is mediated by nitric oxide (NO). Iron redistribution inhibits growth of tumor cells and microorganisms and may also enhance cytokine effects (Fig. 15), whereas iron availability for Hb synthesis is reduced . 34 Disturbances of Iron Metabolism/Erythropoiesis Iron Redistribution in ACD IFN'"'!.
Similar pathological mechanisms are also at the root of lead-induced anemia and disturbance of porphyrin synthesis. Chronic lead intoxication leads to inhibition of o-aminolevulinic acid dehydratase and of ferrochelatase. All the above-mentioned causes ultimately produce a disturbance of iron utilization via the synthesis of an incomplete porphyrin skeleton or via the direct inhibition of ferrochelatase, with the general features of sideroachrestic (sideroblastic) anemia described above. If the defect is mainly in the terminal stage of the reaction (incorporation of iron by ferrochelatase), zinc is incorporated into the finished protoporphyrin skeleton instead of iron, recognizable from the increased concentration of Zn-protoporphyrin in the erythrocytes.